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New Investigator Lecture with David Veesler, PhD
March 3 @ 11:00 am - 12:00 pm
“Structure-guided design of SARS-CoV-2 subunit vaccines”
The emergence of SARS-CoV-2 coronavirus at the end of 2019 resulted in the ongoing COVID-19 pandemic, bringing the world to a standstill. A few weeks after the first SARS-CoV-2 isolate was sequenced, my lab demonstrated that ACE2 is a functional receptor and provided atomic-level information of the viral spike infection machinery which provided a blueprint used by thousands of groups worldwide for the design of vaccines and inhibitors. To understand the immune response towards SARS-CoV-2, we carried out a large-scale serological analysis of COVID-19 patient cohorts and revealed that the viral spike receptor-binding domain is immunodominant and accounts for 90% of the serum neutralizing activity. We structurally defined a spike antigenic map and serologically quantified serum antibodies specific for distinct epitopes leading to the identification of two major sites which correlate with neutralizing antibody titers. Based on this work, we designed a subunit vaccine multivalently displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array using a self-assembling protein nanoparticle which induces potent and protective neutralizing antibody responses in mice and non-human primates. This vaccine is currently evaluated in clinical trials.